The objective of this research is to reduce the cost and increase the rate of DNA sequencing. The specific aims are a ten-fold reduction in the cost of DNA purification for sequencing and fully automated throughput of up to 960 samples per day (per instrument) at the end of twenty-four months. The technology is based on the array microcentrifuge, a powerful new development in centrifugation which for the first time permits completely automated centrifuge-based biological or chemical protocols. The technology is already capable of producing sequence-ready DNA templates at greatly reduced cost. The specific aims of this research will be achieved by testing and refining the microarray centrifuge in production scale sequencing environments so as to produce a technology which will make an impact on the progress of the Human Genome Project and all subsequent genome sequencing efforts. Four instruments will be installed and fully operational in genome centers by the end of year one. The success of the proposed research is defined herein by specific measures of instrument reliability and DNA sequence quality. The primary method used to achieve the aims is the repeated loop of testing on a limited production scale, structured feedback, and re-design or protocol refinement. Each time through this loop, the production scale will be increased to expose weaknesses in the technology so they may be eliminated for the next iteration. Structured input is solicited from the test labs in year two to allow for changes in direction in the field of de novo sequencing. Lastly, the application provides for training and support materials to facilitate the transfer of the technology to the broader genomics community during year two.